GW182 Proteins Restrict Extracellular Vesicle-Mediated Export of MicroRNAs in Mammalian Cancer Cells

Ghosh, Souvik; Mukherjee, Kamalika; Chakrabarty, Yogaditya; Chatterjee, Susanta; Ghoshal, Bartika; Bhattacharyya, S. N.

doi:10.1128/mcb.00483-20

Cited by 9 publications

(7 citation statements)

References 52 publications

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“…But how miR-146a gets differentially exported out of infected macrophage cells is a fascinating question. Retention of miRNA and their targets with polysomes has been found to be the reason for reduced miRNA export noted in mammalian cells (Ghosh et al, 2015) while target RNA presence positively influences the export process (Ghosh et al, 2021). We have isolated the polysomes from control and infected cells and detected increased retention of both miR-146a and miR-155 with polysomes in the infected cells (Supplementary Figure 5A, D).…”

Section: Leishmania By Targeting Hur Ensures Export Of Mir-146a But Not Mir-155 From the Infected Cellsmentioning

confidence: 79%

Leishmania Hijacks microRNA Import-Export Machinery of Infected Macrophage and Survives by Cross-Communicating Host miR-146a to Subjugate HuR and miR-122 in Neighbouring cells

Ganguly

Ghoshal

Banerji

et al. 2021

Preprint

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Leishmania donovani, the causative agent of visceral leishmaniasis, infects and resides within tissue macrophage cells of the mammalian host. It is not clear how the parasite infected cells cross-talk with the non-infected cells in the infection niche to regulate the infection process. Interestingly, miRNAs, the regulatory small RNAs of the host, could get trafficked into and out of infected cells as part of extracellular vesicles to ensure exchange of the epigenetic signals and can regulate the expression of their target genes in both donor and recipient cells. Leishmania, for its survival in host macrophage, adopts a dual strategy to regulate the intercellular transport of host miRNAs. The parasite, by preventing mitochondrial function of the host cells, restricts the entry of liver cell derived miR-122 containing extracellular vesicles in infected macrophage to curtail the inflammatory response by miR-122. The parasite reciprocally upregulates the extracellular export of anti-inflammatory miR-146a from the infected cells. The exported miR-146a restricts miR-122 production in liver cells and polarizes neighbouring naïve macrophages to the M2 state by targeting RNA Binder protein HuR.

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Section: Leishmania By Targeting Hur Ensures Export Of Mir-146a But Not Mir-155 From the Infected Cellsmentioning

confidence: 79%

Leishmania Hijacks microRNA Import-Export Machinery of Infected Macrophage and Survives by Cross-Communicating Host miR-146a to Subjugate HuR and miR-122 in Neighbouring cells

Ganguly

Ghoshal

Banerji

et al. 2021

Preprint

Self Cite

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show abstract

“…But how miR-146a gets differentially exported out of infected macrophage cells is a fascinating question. Retention of miRNA and their targets with polysomes has been found to be the reason for reduced miRNA export noted in mammalian cells ( Ghosh et al, 2015 ), whereas target RNA presence positively influences the export process ( Ghosh et al, 2021 ). We have isolated the polysomes from control and infected cells and detected increased retention of both miR-146a and miR-155 with polysomes in the infected cells ( Fig S5A and D ).…”

Section: Resultsmentioning

confidence: 99%

Leishmania survives by exporting miR-146a from infected to resident cells to subjugate inflammation

et al. 2022

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Leishmania donovani, the causative agent of visceral leishmaniasis, infects and resides within tissue macrophage cells. It is not clear how the parasite infected cells crosstalk with the noninfected cells to regulate the infection process. During infection, Leishmania adopts a dual strategy for its survival by regulating the intercellular transport of host miRNAs to restrict inflammation. The parasite, by preventing mitochondrial function of host cells, restricts the entry of liver cell derived miR-122–containing extracellular vesicles in infected macrophages to curtail the inflammatory response associated with miR-122 entry. On contrary, the parasite up-regulates the export of miR-146a from the infected macrophages. The miR-146a, associated with the extracellular vesicles released by infected cells, restricts miR-122 production in hepatocytes while polarizing neighbouring naïve macrophages to the M2 state by affecting the cytokine expression. On entering the recipient macrophages, miR-146a dominates the miRNA antagonist RNA-binding protein HuR to inhibit the expression of proinflammatory cytokine mRNAs having HuR-interacting AU-rich elements whereas up-regulates anti-inflammatory IL-10 by exporting the miR-21 to polarize the recipient cells to M2 stage.

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“…The interaction of miRNA and mRNA may be modulated in mammalian cells. In the presence of target mRNA, miRNAs are prone to delivery by MVB-secreted exosomes and this target mRNA-driven miRNA export process was partially retarded by Argonaute 2 (Ago2)-interacting protein GW182B [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Circulating Small Extracellular Vesicle-Derived miR-342-5p Ameliorates Beta-Amyloid Formation via Targeting Beta-site APP Cleaving Enzyme 1 in Alzheimer’s Disease

Dong

Gu²,

Guo

et al. 2022

Cells

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Alzheimer’s disease (AD) is a common neurodegenerative disorder with progressive cognitive impairment in the elderly. Beta-amyloid (Aβ) formation and its accumulation in the brain constitute one of the pathological hallmarks of AD. Until now, how to modulate Aβ formation in hippocampal neurons remains a big challenge. Herein, we investigated whether the exosomal transfer of microRNA (miR) relates to amyloid pathology in the recipient neuron cells. We isolated circulating small extracellular vesicles (sEVs) from AD patients and healthy controls, determined the miR-342-5p level in the sEVs by RT-PCR, and evaluated its diagnostic performance in AD. Then, we took advantage of biomolecular assays to estimate the role of miR-342-5p in modulating the amyloid pathway, including amyloid precursor protein (APP), beta-site APP cleaving enzyme 1 (BACE1), and Aβ42. Furthermore, we subjected HT22 cells to the sEVs from the hippocampal tissues of transgenic APP mice (Exo-APP) or C57BL/6 littermates (Exo-CTL), and the Exo-APP enriched with miR-342-5p mimics or the control to assess the effect of the sEVs’ delivery of miR-342-5p on Aβ formation. We observed a lower level of miR-342-5p in the circulating sEVs from AD patients compared with healthy controls. MiR-342-5p participated in Aβ formation by modulating BACE1 expression, specifically binding its 3′-untranslated region (UTR) sequence. Exo-APP distinctly promoted Aβ42 formation in the recipient cells compared to Exo-CTL. Intriguingly, miR-342-5p enrichment in Exo-APP ameliorated amyloid pathology in the recipient cells. Our study indicated that miR-342-5p was dysregulated in human circulating sEVs from AD patients; sEV transfer of miR-342-5p ameliorates Aβ formation by modulating BACE1 expression. These findings highlight the promising potential of exosomal miRNAs in AD clinical therapy.

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GW182 Proteins Restrict Extracellular Vesicle-Mediated Export of MicroRNAs in Mammalian Cancer Cells

Cited by 9 publications

References 52 publications

Leishmania Hijacks microRNA Import-Export Machinery of Infected Macrophage and Survives by Cross-Communicating Host miR-146a to Subjugate HuR and miR-122 in Neighbouring cells

Leishmania Hijacks microRNA Import-Export Machinery of Infected Macrophage and Survives by Cross-Communicating Host miR-146a to Subjugate HuR and miR-122 in Neighbouring cells

Leishmania survives by exporting miR-146a from infected to resident cells to subjugate inflammation

Circulating Small Extracellular Vesicle-Derived miR-342-5p Ameliorates Beta-Amyloid Formation via Targeting Beta-site APP Cleaving Enzyme 1 in Alzheimer’s Disease

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